DESCRIPTION (provided by investigator): This applications is a Competitive Revision to R01 CA67262, entitled "Premenopausal Hormone Levels and Risk of Breast Cancer", in response to NOT-OD-09-058, "The Availability of Recovery Act Funds for Competitive Revision Applications". The parent grant funds the assessment of a range of premenopausal hormones (e.g., plasma sex steroids) in relation to breast cancer risk in the Nurses'Health Study II (NHSII) cohort. The NHSII cohort consists of 116,430 women who have been followed biennially by questionnaire since 1989. Between 1996 and 1999 (and funded by CA67262), we collected blood and urine samples from 29,611 NHSII participants. In the current application, we propose to collect a second set of blood and urine samples from these women, which will substantially enhance the ability to examine biomarker exposures at different points in life in relation to cancer risk. Women were 32 to 54 years old at the first collection and were predominantly premenopausal;they will be 46 to 66 years old and predominantly postmenopausal at the time of the proposed collection. The collection of a second set of biospecimens from NHSII women would form one of the only large biorepository in the world to have samples from the same women 10-15 years apart;we anticipate based on prior biospecimen collection response rates to obtain samples from over 19,000 women. Further, many of the sample sets would be paired pre- and postmenopausal samples (n~13,000 women). With continued follow-up of the cohort, we would be in a unique position to assess temporal associations between biomarkers and disease risk, which has particular relevance to cancer given its multi-stage carcinogenic process. In addition, having a mid-life sample and a sample in later life will assist in determining the importance of age in modifying biomarker-disease relationships. Further, of substantial interest in breast cancer research is whether endogenous hormones measured during pre- and post menopause are independently associated with breast cancer risk, and whether potential interactions exist between the two. This application meets the goals of the American Recovery and Reinvestment Act by hiring three new staff members, purchasing equipment from a U.S. company, and using another U.S. company to mail blood collection kits and process the returned samples. Ultimately, this resource would lead to the development of scientific aims for future grants that would address important scientific questions, create new jobs, provide continuing support for existing personnel, and create a powerful biorepository for studying associations between biomarkers and disease in women. PUBLIC HEALTH RELEVANCE: This project would create a blood and urine repository in the Nurses'Health Study II containing samples from the same women collected about 10 to 15 years apart, nearly 70 percent of which would be paired pre- and postmenopausal samples. This resource could be used to answer important scientific questions relating to biomarker exposures and cancer risk, to better understand how cancer develops and identify potential prevention methods.